Inflammatory blood markers show moderate power to predict pneumonia after stroke

Stroke survivors who go on to develop pneumonia show measurably higher levels of several circulating inflammatory markers within 24 hours of the stroke, before any diagnosis of infection, according to a systematic review and meta-analysis published in the European Journal of Medical Research. The work, registered prospectively with PROSPERO and conducted under PRISMA guidelines, pooled data from 49 studies covering 22,796 patients to ask a deceptively simple question: can routine blood-based inflammation measures flag post-stroke pneumonia early enough to matter?

Post-stroke pneumonia is one of the most serious complications of acute stroke, yet the review's authors note that the field lacks robust tools for ultra-early prediction.

The analysis compared patients who developed pneumonia with those who did not, using blood samples drawn within 24 hours of stroke onset and before any pneumonia diagnosis. Patients who later developed the complication had higher levels of the systemic inflammation response index (SIRI), the systemic immune-inflammation index (SII), the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR), the monocyte-to-lymphocyte ratio (MLR), interleukin-6, lipopolysaccharide-binding protein, D-dimer, and fibrinogen than controls.

Association alone does not establish independent predictive value, so the researchers also examined adjusted odds ratios per one-unit increase in each marker. After this adjustment, SIRI and NLR remained significantly associated with post-stroke pneumonia. MLR was nominally significant before but not after Benjamini-Hochberg correction for multiple testing. SII and PLR showed no significant association, which the authors attribute to the scale of these composite indices, while the lymphocyte-to-monocyte ratio failed to reach significance owing to statistical imprecision. The prognostic nutritional index could not be pooled at all.

For prediction, the team pooled the area under the receiver-operating characteristic curve, a standard measure of how well a test discriminates between patients who will and will not experience an outcome. NLR performed best, with a pooled AUC of 0.78, followed closely by MLR at 0.77. SII and SIRI both reached 0.73. These values fall in the range conventionally described as moderate discrimination, meaning the markers carry real signal but are not accurate enough on their own to serve as stand-alone diagnostic tools.

Statistical rigor varied across the panel of markers. After Benjamini-Hochberg correction, 16 of 21 primary analyses remained significant, a proportion the authors report transparently rather than overclaiming. Study quality was assessed with the Newcastle-Ottawa Scale, and prediction studies were additionally evaluated with PROBAST, a tool designed specifically to gauge risk of bias in prediction-model research.

The searches spanned PubMed, Web of Science, the China National Knowledge Infrastructure, and Wanfang Data, giving the review a broad international evidence base. Even so, the authors emphasize that substantial residual heterogeneity persisted across studies, and that optimal cut-off values for the biomarkers varied considerably, complicating any attempt to translate the pooled estimates directly into clinical thresholds.

The conclusion the authors draw is deliberately cautious. Several inflammatory biomarkers were significantly associated with post-stroke pneumonia and showed moderate predictive value, but given the moderate discrimination, the variability in cut-offs, and the residual heterogeneity, they characterize the findings as hypothesis-generating. Whether dynamic biomarker monitoring adds value to existing clinical prediction tools, they write, remains to be established in prospective multicenter studies.

For clinicians and researchers, the meta-analysis offers a consolidated map of which blood markers have repeatedly tracked with early pneumonia risk after stroke, and which have not survived adjustment or correction. It does not endorse any single marker for bedside use. Instead, it sets the agenda for the next step: prospective, multicenter studies that test whether measuring these indices in the first hours after stroke, alongside established clinical scores, genuinely improves early identification of patients at risk of post-stroke pneumonia.

Subject of Research: Inflammatory biomarkers as predictors of post-stroke pneumonia

Article Title: Association and predictive performance of inflammatory biomarkers for post-stroke pneumonia: a systematic review and meta-analysis

Article References: Liu, M., Zeng, N., Zhao, X., Liu, P., & Liu, P. (2026). Association and predictive performance of inflammatory biomarkers for post-stroke pneumonia: a systematic review and meta-analysis. European Journal of Medical Research. https://doi.org/10.1186/s40001-026-05390-w

Image Credits: AI Generated

DOI: 10.1186/s40001-026-05390-w

Keywords: stroke, post-stroke pneumonia, inflammatory biomarkers, meta-analysis, NLR, SIRI, systematic review, predictive value, AUC, PROSPERO, interleukin-6, immune response